Vitamin E, known also as .alpha.-tocopherol, of formula ##STR2## is an important nutritional factor both for humans and animals, endowed with antioxidizing activity that protects the cells from the oxidation and therefore from the degeneration. It is present in nature in vegetable oils and legumes and is produced also by chemical synthesis. The total synthesis of vitamin E, described from H. Mayer et al. in Helvetica Chimica Acta, 46, 650, (1963), is carried out by means of the Wittig's condensation between the aldehydic derivative A having chromanic structure and the phosphonium salt of an alkyl derivative having 15 carbon atoms (compound B), obtained by chemical modification of the natural compound phytol, and subsequent hydrogenation of the double bond between the positions 1' and 2' as reported in the hereinbelow Scheme 1. ##STR3## J. W. Scott et al. in Helvetica Chimica Acta 59, 290-306, (1976) show an alternative synthetic, method wherein the Wittig's reaction is used for the formation of the carbon-carbon bond between positions 2'-3' instead of between positions 1'-2' as reported in the hereinbelow Scheme 2. ##STR4##
The synthesis requires the preparation of a chromanic synthon (D) superior homologue (Scheme 3) and of an alkyl residue (E) inferior homologue (Scheme 4) in respect of those described from H. Mayer et al., always through a series of reactions quite complex and little convenient both from a practical and an economical point of ##STR5##
Both described methods described hereinabove provide for the introduction of a functionalization of aldehydic type on the chromanic residue that requires a high number of reactions with considerable disadvantages both from the practical point of view and in terms of yield and of a functionalization of halide type on the alkyl residue, with the aim to allow a synthetic approach by means of the Wittig's reaction, also remarkably complicated and therefore little practical and poorly profitable from an industrial point of view. An alternative synthetic strategy that better complies with criteria of practicality and economy can be drafted by considering the preparation of a functionalization of halide type on the residue with chromanic structure with the aim to arrange for the preparation of the phosphonium salt useful for the Wittig's condensation reaction. The halide derivatives on the residue with chromanic structure of formula I ##STR6## are not known and form the object of the present invention together with the process to obtain them. A further advantage of this alternative method is represented by the fact that the aliphatic chain has to be functionalized by means of an aldehydic group and that this aldehydic derivative can be obtained from the phytol by means of a series of reactions lower in respect to the series of reactions necessary to get the [B] or [E] aliphatic derivatives. A further application of the compounds of formula I is possible in the synthesis of compounds with benzopyranic structure having side chain different from that of vitamin E, but endowed with similar properties, antioxidizing and inhibiting the formation of lipid peroxides recently reported in literature, for instance from P. A. McCarthy in Med. Res. Rew. 13, 135-159, (1993). Such derivatives can easily be synthesized by utilizing the chemical reactivity of the alkylhalide functional group in side chain to the chromanic residue present in the compounds of general formula I that forms the object of the present invention. One of these products is troglitazone, also known as CS-045, which is part of a series of derivatives having benzylthiazolidinic structure of general formula ##STR7## endowed with properties inhibiting the formation of lipidic peroxides, proposed in the therapy and prevention of atherosclerosis and of diabetic complications caused by processes of lipidic peroxidation and described in U.S. Pat. No. 4,873,255. The synthetic method used for the preparation of the troglitazone of formula ##STR8## described in Drugs of the Future, 14, 847, (1989) and in U.S. Pat. No. 4,873,255 provides for two alternative routes illustrated in Schemes 5 and 6. ##STR9##
The starting material of the first mute is represented by trelox, 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid, described in the literature and used as antioxidizer. Troglitazone, at present clinically tested as antidiabetic and antiatherosclerotic, is prepared (Scheme 5) by reduction of the carboxy group in position 2 to alcoholic group, subsequent protection of the hydroxylic group of phenolic type, condensation with 4-nitro-chlorobenzene, substitution of the protective group on the phenolic hydroxyl with the acetyl group, reduction of the nitro group, condensation with ethyl acrylate through an intermediate diazonium salt and lastly cyclization with thiourea. The alternative route (Scheme 6) instead provides starting product a suitably substituted acetophenone obtainable starting from the trimethylhydroquinone with a series of known reactions and from which by cyclization with 4-nitrophenoxyacetone the chromanic derivative substituted in position 2 is obtained which by subsequent reduction of the carbonyl in position 4, dehydration of the obtained alcohol and contemporary reduction of the double bond and of the nitro group in side chain allows to get the aminic intermediate already considered in the previous Scheme. The process described for the preparation of the compounds of general formula I object of the present invention is certainly more practical and less complicated of those previously described for the synthesis of the intermediates of the vitamin E and of the troglitazone and therefore the claimed derivatives result extremely effective intermediates for a process of industrial manufacture more advantageous of these two drugs. Moreover they can represent valid starting compounds for the synthesis of molecules analogous to vitamin E endowed with antioxidizing properties, useful in fields other than the pharmaceutical field, like in the stabilization of the plastics to the oxidizing agents or in the conservation of foodstuffs.